Transcranial Magnetic Stimulation (TMS) has been used diagnostically for a very long time in velocity of conduction in cortico-spinal tracts and peripheral nerves as well as intra-operative monitoring. For example, see Rossini, P. M. and R. Simone, “Transcranial magnetic stimulation: Diagnostic, therapeutic, and research potential,” Neurology, 68:484-488, 2007, which describes the use of TMS for the noninvasive investigation of nerve propagation along the corticospinal tract, spinal roots, and peripheral nerves in humans, including mapping of motor output, and intra-operative monitoring.
Jean-Pascal Lefaucheur and colleagues have examined repetitive Transcranial Magnetic Stimulation (rTMS) of the motor (pre-central) cortex for pain relief (Lefaucheur, J.-P., Drouot, X., Keravel, Y., and J.-P. Nguyen, “Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex,” Neuroreport: 17 Sep. 2001, 12:13, pp. 2963-2965, and Lefaucheur, J.-P., Hatem, S., Nineb, A., Ménard-Lefaucheur, I., Wendling, S., Keravel, Y., and J.-P. Nguyen, “Somatotopic organization of the analgesic effects of motor cortex rTMS in neuropathic pain,” Neurology 67:1998-2004, 2006). Lefaucheur (“Use of repetitive transcranial magnetic stimulation in pain relief,” Expert Review of Neurotherapeutics, May 2008, Vol. 8, No. 5, Pages 799-808, DOI 10.1586/14737175.8.5.799 (doi: 10.1586/14737175.8.5.799) notes that a subset of patients will get relief from rTMS but relapse and for those patients surgically implanted epidural cortical electrodes and associated pulse generator can be proposed to allow pain relief more permanent, and that the rate of improvement due to rTMS may be predictive of the outcome of such an implantation.
In the early 1990s, Mark George and colleagues described the antidepressant effect of rTMS when applied to the left dorsolateral prefrontal cortex. Since that time, rTMS has become a recognized as an effective method for treating depression. One rTMS device (NeuroStar system by Neuronetics Inc, Malvern, Pa.) has received FDA clearance for marketing for the treatment of depression.
In all of the TMS procedures and devices described above are limited to use of a single coil intended to directly affect a superficial cortical brain region, with unspecified downstream effects within the network. Not surprisingly, the site of primary stimulation on the superficial cortex is typically more affected by rTMS stimulation than are sites which are synaptically connected (“downstream connections) with the primary stimulation site. However, many disorders and symptoms of disorders may benefit from direct neuromodulation of deeper brain target regions. Described herein are devices and methods for deep-brain neuromodulation that may address many of the shortcomings described above.
Deep-brain neuromodulation for therapeutic purposes is well known using either focused (U.S. Pat. No. 7,520,848 and PCT/US2007/010262) or non-focused (U.S. Pat. No. 7,407,478) approaches. However, it remains highly desirable to use TMS for deep-brain neuromodulation in a manner that does not significantly stimulate intervening, non-target regions of the brain (e.g., between the electromagnet(s) and the deep-brain targets). For example, the use of a non-focused TMS electromagnet as described in U.S. Pat. No. 7,407,478 requires higher stimulation at regions of the brain more superficial (e.g., superficial cortical brain regions between the deep brain target and the magnet) than at the deep brain target. We herein propose a solution to this problem by using a specific methodology and device as described herein in order to take advantage of spatial summation of intrinsic brain networks in order to achieve selective deep brain modulation in a manner not previously suggested.
Deep-brain stimulation may be achieved by direct stimulation (e.g., by the direct application of a magnetic field) of the deep brain target, and/or by the indirect stimulation of the deep brain target region by spatial summation at the deep-brain target from more superficial brain regions (including superficial cortical sulci and gyri brain regions near the skull). Described herein are methods including the use of multiple TMS electromagnets that may provide deep-brain stimulation by enhanced spatial summation of resulting in stimulation of one or more deep-brain regions. The deep-brain stimulation described herein may be used in addition to, or in place of, direct deep-brain TMS.